Poly N-acetyllactosamine substitutions on N- and not O-oligosaccharides or Thomsen-Friedenreich antigen facilitate lung specific metastasis of melanoma cells via galectin-3.
Galectin-3 on vascular endothelium has been shown to facilitate lung specific metastasis. Metastatic variants of B16 melanoma were chosen to identify specific ligands that mediate lung colonization via galectin-3. Flow cytometry showed that, galectin-3 binding to cells correlates with surface expression of poly N-acetyllactosamine (polylacNAc) but not with other reported ligands, e.g. Thomsen-Friedenreich (T/Tn) antigen. Immobilized galectin-3 promoted adhesion of melanoma cells in a metastasis dependent manner. Moreover, adhesion and galectin-3 binding to cells were specifically inhibited with lactose. These properties together with lung metastasis were inhibited with N-glycosylation inhibitor Swainsonine (SW), whereas, O-glycosylation inhibitor Benzyl-alpha-N-acetylgalactosamine (BG) had no effect. BG treatment significantly increased expression of T/Tn antigen on low metastatic cells; however, had no effect on their metastatic potential. The studies very comprehensively demonstrate the importance of polylacNAc substitutions on N-oligosaccharides in galectin-3 mediated lung metastasis.
Srinivasan
Nithya
N
Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210, India.
Bane
Sanjay M
SM
Ahire
Shashikant D
SD
Ingle
Arvind D
AD
Kalraiya
Rajiv D
RD
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001593:Benzyl Compounds / Q000494:pharmacology; D019921:Biotinylation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D055767:Immobilized Proteins; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects
D015295:Antigens, Tumor-Associated, Carbohydrate; D001593:Benzyl Compounds; D037502:Galectin 3; D055767:Immobilized Proteins; D009844:Oligosaccharides; D011134:Polysaccharides; C016467:Thomsen-Friedenreich antigen; C080739:benzyl-alpha-N-acetylgalactosamine; C037199:poly-N-acetyllactosamine; D000116:Acetylgalactosamine